Abstract Mutations initiate and facilitate the progression of a multitude of human diseases, especially cancer and neurodegenerative diseases; and mutagenic repair of DNA damage contributes to aging. The 2008 Gordon Research Conference on Mutagenesis will focus on the molecular mechanisms of mutagenesis that give rise to genomic instability. The goals of this meeting are (1) to explore current knowledge of mutagenesis mechanisms; (2) to identify new avenues of investigation; (3) to define therapeutic strategies for maintenance of genomic integrity; (4) to stimulate collaborations; and (5) to foster the long-term development of this critical research area. The program will specifically focus on advances that provide mechanistic understanding of pathways that maintain the integrity of the human genome, with emphasis on how these pathways intersect genetic disease, cancer, neurodegeneration and aging. The eight sessions will consider: (i) Mutagenesis Due to Blocked Replication and Transcription, (ii) Consequences of Oxidative Stress, (iii) Recombination Induced Genomic Instability, (iv) Physiological Mutagenesis in the Immune Response, (v) Rare Human Diseases Associated with Genomic Instability, Neurodegeneration and Premature Aging, (vi) Low-fidelity Replication and Cancer, (vii) Mechanisms of Mutagenesis, and (viii) Mismatch Repair: the Final Fidelity Check. The molecular and mechanistic emphasis on pathways critical in a variety of biological contexts is designed to attract a unique audience of researchers and propel their future research.